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Tumor Metastasis with a Twist
Newswise, March 16, 2011 — In the early
stages of human embryogenesis, a
transcription factor called Twist1 plays a
key regulatory role in how the embryo
assumes form and function. Much later in
life, however, researchers at the University
of California, San Diego School of Medicine,
say Twist1 can re-emerge, taking a darker
and more deadly turn.
In a paper published in the March 15, 2011
issue of Cancer
Cell, UCSD scientists led by Jing Yang,
PhD, assistant professor of pharmacology and
pediatrics, identify a unique function of
Twist1 in later life: it promotes the
formation of invadopodia in tumor cells, a
vital step in the spread of such cells
(metastasis) to surrounding tissues and
other parts of the body.
Invadopodia (meaning “invasive feet”) are
tiny protrusions of tumor cells that extend
into the extracellular matrix – the
surrounding connective tissue and fibers
that provide support. Invadopodia
concentrate enzymes that degrade the matrix
so that tumor cells can break away and
Previous studies have linked the expression
of Twist1 to many aggressive, solid-tumor
cancers, including melanomas, neuroblastomas,
as well as breast and prostate cancer.
The new research by Yang and colleagues
describes in detail how Twist1 initiates the
multi-step pathway resulting in invadopodia
formation and matrix degradation. The
research also reveals places in the process
that may present potential targets for
future anti-metastasis therapies.
After embryogenesis, Twist1 is normally
suppressed. Cancer cells, however,
reactivate the transcription factor,
enabling Twist1 to initiate its complex
pathway leading to metastasis.
Drug designers, however, have yet to
successfully devise a way to directly
inhibit transcription factors like Twist1.
The UCSD study points to other
“We hope to inhibit downstream targets of
Twist1 (such as platelet-derived growth
factor receptors) to inhibit invadopodia
formation and function,” Yang said.
“Our study suggests that inhibition of
invadopodia-mediated matrix degradation
could be an effective way to suppress
If that happens, a cancer tumor becomes a
stable, unmoving and easier target for other
types of therapeutic treatments.
Co-authors of the paper include Mark A.
Eckert and Andrew T. Chang, UCSD Molecular
Pathology Graduate Program and Biomedical
Science Graduate Program; Thinzar M. Lwin
and Etienne Danis, UCSD Department of
Pharmacology; and Jihoon Kim and Lucila Ohno-Machado,
UCSD Division of Biomedical Informatics.
Research funding came, in part, from the
National Institutes of Health, the Sydney
Kimmel Foundation for Cancer Research, the
California Breast Cancer Research Program
and the Susan G. Komen Foundation.